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Pharmaceutical composition reversing resistance of hepatoma carcinoma cells to sorafenib

A drug and mixture technology, applied in the field of cell biology and medical treatment, can solve the problems of difference in curative effect and low drug response rate

Inactive Publication Date: 2019-06-04
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although sorafenib can improve the 3-month survival time and radiological progression-free period of the patients in the phase III clinical trial, the study shows that the response rate of the patient to the drug is relatively low, and the efficacy has obvious individual differences

Method used

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  • Pharmaceutical composition reversing resistance of hepatoma carcinoma cells to sorafenib
  • Pharmaceutical composition reversing resistance of hepatoma carcinoma cells to sorafenib
  • Pharmaceutical composition reversing resistance of hepatoma carcinoma cells to sorafenib

Examples

Experimental program
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Effect test

Embodiment 1

[0013] Detection of expression levels of enzymes related to prostaglandin synthesis pathway in human liver cancer cell line HepG2 and acquired drug-resistant cell lines.

[0014] Human liver cancer cell line HepG2 and drug-resistant cell line (HepG2-R) were inoculated into 6-well plates, cultured in DMEM medium containing 10% fetal bovine serum, and cultured in an incubator at 37°C and 5% CO2 saturated humidity. Grow to cover more than 80% of the culture, add Trizol to lyse the cells, extract total RNA according to the literature "Single Step Method of RNA Isolation by Acid Guanidinium Thiocyanate-Phenol-Chloroform Extraction", use real-time fluorescent quantitative PCR method according to the literature "Targeting KDM1A attenuates Wnt / β-catenin signaling pathway to eliminate sorafenib-resistant stem-like cells in hepatocellular carcinoma” operating conditions to detect changes in gene mRNA levels of drug-resistant strains AKR1C2 and AKR1C3, the final results are as follows f...

Embodiment 3

[0016] Example 3 Sorafenib combined with prostaglandin synthesis pathway inhibitor inhibits the growth of HepG2 cells.

[0017] The HepG2 drug-resistant cell line was inoculated into a 96-well plate for culture, and 24 hours after inoculation, the cells were cultured with different concentrations of sorafenib and prostaglandin synthesis pathway inhibitors for 24 hours, and CellTiter- Luminescent CellViability Assay analyzes the trend of cell proliferation, the final result is as follows image 3 As shown, the combination of sorafenib (5 μM) and FLU (10 μM) can significantly inhibit cell proliferation.

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Abstract

The invention relates to a pharmaceutical composition, and relates to inhibitors Aspirin and Flufenamic acid of a key enzyme AKR1C3 in a prostaglandin synthesis pathway, wherein the inhibitors can reverse the resistance of hepatoma carcinoma cells to sorafenib at low concentration in cooperation with sorafenib. An adopted specific method is an effective method that the AKR1C3 inhibitors Aspirin and Flufenamic acid and low-concentration sorafenib act together on sorafenib-resistant HepG2 hepatoma cell lines and can significantly inhibit the growth of sorafenib-resistant HepG2 cells, so as to overcome the sorafenib resistance.

Description

technical field [0001] The invention discovers a new target for reversing the drug resistance of liver cancer cells-inhibiting the prostaglandin synthesis pathway, and belongs to the field of cell biology and medical technology. Background technique [0002] Liver cancer is one of the most common malignant tumors, with extremely high morbidity and mortality in my country. At present, in clinical diagnosis and treatment of liver cancer, there are serious problems such as difficulty in early diagnosis, low rate of surgical resection (15%-25%), high rate of recurrence and metastasis (20%-60%), and lack of targeted treatment. Therefore, molecular targeted therapy has become one of the important methods in the comprehensive treatment of liver cancer in recent years. Sorafenib, an effective RAF kinase inhibitor, is the only molecularly targeted drug approved by the FDA for the clinical treatment of liver cancer. By inhibiting the activity of vascular endothelial growth factor re...

Claims

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Application Information

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IPC IPC(8): A61K31/616A61K31/196A61K31/44A61P35/00
Inventor 刘扬孙铭菊
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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